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Dealing with drugs

A young girl treated for sleeping sickness lies on a bed, accompanied by her grandmother in Katanda THA centreBenoit Marquet

02Mar
2015

While Ebola makes the headlines, a raft of unreported and under-researched diseases are responsible for far more deaths across Africa every year. But without adequate financial rewards for the West, too little is being done to help

Have you heard about the outbreak of a sometimes fatal disease that saw 8,600 cases in one African country alone in 2014? There was another, smaller, outbreak in December. The same disease saw 18,000 cases between 2009 and 2011 in South Africa.

That country is the giveaway: we’re not talking about Ebola. In this instance the disease was measles, which killed 122,000 people in 2012, according to the World Health Organization, and affects more than 20 million people every year.

Grim mortality statistics are not the only way in which measles puts the current outbreak of Ebola into perspective. Many scientists, campaigners and aid workers are quick to point out that the global reaction to Ebola – and the indecent haste to manufacture a vaccine – says much about the way in which the West’s health priorities trump those in developing countries.

At least all of us will have heard of measles. But it is one of just many diseases – at least 20 according to the WHO – that take an inexorable toll on developing nations, particularly in Africa. Unlike Ebola, there is no discernible political momentum to devise a vaccine for most of them.

They include leishmaniasis, which occurs in 98 countries and causes 40,000 deaths a year; elephantiasis which has left 40 million disfigured or incapacitated; and Chagas disease which is endemic to Latin America and kills more people in the region each year than any other parasite-born disease, including malaria.

HYSTERICAL RESPONSE

The point is not to in any way downplay the seriousness, the ghastliness of Ebola, or the way in which it has ravaged Guinea, Sierra Leone and Liberia, and its potential to wreck havoc beyond West Africa. But why, a cynic might ask, has such impetus developed in the wake of a very small number of deaths in the US and Europe? The hysteria was perhaps best illustrated by the experience of a healthy boy from Sierra Leone banned from taking up a placement at a primary school in Greater Manchester amid fears he might transmit the virus.

‘Being cynical is a reasonable position to take,’ says Mohga Kamal-Yanni, senior health policy adviser at Oxfam. ‘Although we have known about Ebola for 40 years, the number of people affected has always been small. The more important factor is that there is no commercial market. That’s why we get Viagra developed but not a vaccine for Ebola. But if people are coming back ill to the West, then there becomes a commercial market.’

‘It’s true,’ says Julien Potet, neglected tropical diseases policy adviser at Médecins Sans Frontières. ‘Ebola only became big in the news when it attracted the spotlight of ex-pats falling ill.’ This, he says, reflects a wider picture where, in the past ten years, ‘the drugs developed for tropical diseases have generally been justified on the grounds they are a threat to citizens in the West.’

Drugs for Neglected Diseases (DNDi), a non-profit research and development organisation developing new treatments for neglected diseases and supported by Médecins Sans Frontières, has calculated that, of the 1,556 new drugs approved between 1975 and 2004, only 21 (1.3 per cent) were specifically developed for tropical diseases and tuberculosis, even though these diseases account for 11.4 per cent of the global disease burden.

A community health worker uses a mobile device to test for malaria in the village of Nanso Takorasi, Ghana (Image: Jonathan Torgovnik)

MARKET FORCES

Ebola also tapped into deep, core fears in the West, according to Professor Melissa Leach, director of the Institute of Development Studies at the University of Sussex. ‘Ebola has this status of an exceptional disease, the power to attract enormous fear and attention. The nature of the virus – it kills quickly – makes it the stuff of Hollywood movies, emerging from a deep, dark place to threaten the world.’

Yet according to Gregory Härtl, head of public relations for the WHO, there are more nuanced reasons why the West suddenly became more interested in Ebola. ‘This outbreak was qualitatively and quantitatively different from previous ones,’ he says. ‘Ebola has always been 1,000km to the east of this region. The previous outbreak had 450 cases in a confined geographical area, this one spread to densely populated capital cities.’

Yet while the West belatedly demanded a vaccine, the laws of the market meant that further intervention was required. ‘When it comes to pharmaceutical development, it is about profits,’ says Härtl. ‘Various sectors will have different motivations for what they do. We have to work with that. It’s the real world. The pharmaceutical companies will only look at it if there is a market for it; or if there’s no market, at least some other way that will pay for it.’

SOCIAL IMPACTS

DNDi and the WHO have compiled a list of 18 officially neglected diseases, which includes such horrors as sleeping sickness, river blindness and paediatric HIV. Beyond that, there is an unofficial list of what Kamal-Yanni calls ‘super-neglected’ diseases, including a variety of haemorrhagic fevers. ‘They affect small numbers of people – usually – and they come and go,’ she says. Ebola was on this list but has now been upgraded to merely being a ‘neglected’ disease.

Ebola has taken a chronic, debilitating toll on Guinea, Sierra Leone and Liberia in a manner that applies to other tropical diseases. UNICEF says that five million children have missed school in those nations since the outbreak began. ‘The death of parents is a huge problem,’ says Kamal-Yanni. ‘There’s a stigma that reminds me of the HIV orphans. This will still be a problem when Ebola stops and people go back to their communities.’

GDP in all three countries has been cut by up to four percentage points, but the World Bank says that mortality, morbidity, care giving and lost work do not have the greatest economic impact. That honour goes to aversion behaviour, driven by fear of contagion. Citing the case of the SARS epidemic of 2002–2004, and the H1N1 flu epidemic of 2009, the World Bank says that behavioural effects are responsible for up to 90 per cent of the total economic impact of epidemics.

Health care in these countries has disintegrated where it was already fragile at best before; hospitals do not function properly and the WHO sees spikes in what were already high infant and birth mortality rates. ‘There are enormous social issues around people picking up the legacy of Ebola in their communities,’ says Kamal-Yanni. ‘People have been sitting at home, they have no income, food prices have shot up, they borrow and sell to get food. How do you deal with that? We could see bad results.’

Such impacts occur where other neglected diseases break out but do not get reported. The burden ‘is relatively high’ according to Julien Potet. ‘One billion people are thought to suffer from one of the neglected tropical diseases,’ he says. ‘Not all these are fatal, but their burden, their morbidity, their impact on people’s lives is huge. However, they are hardly in the news. They are restricted to areas that no-one hears about, but MSF sees them on a daily basis.’

Vast social and geographical issues are also at play, which determine the extent to which such diseases affect local communities. In the case of Ebola, says Professor Leach, there was a context of longer term issues, of land grabs, mining, a general perception that the government was not acting in the interests of the people.

‘This was a tinderbox,’ she says. ‘A population that was very mobile, health services that were weak, and whatever the government said it was mistrusted. What began as an interaction between a girl in Guinea, a bat and the virus, was the nexus that drew upon decades of vulnerability, poorly-directed aid, and social exclusion.’

EBOLA – A HISTORY

Ebola emerged in 1976 in two simultaneous outbreaks, in Sudan and the Democratic Republic of Congo. The latter occurred in a village near the Ebola River, from which the disease takes its name. Ebola is introduced into the human population through close contact with the blood, secretions, organs or other bodily fluids of infected animals such as fruit bats (thought to be natural Ebola virus hosts), chimpanzees, gorillas, monkeys, forest antelope and porcupines. Health care workers have frequently been infected through close contact with patients and burial ceremonies in which mourners have direct contact with the body of the deceased also play a role.

Ebola gets a prescient mention in Redmond O’Hanlon’s classic travel book of 1996, Congo Journey, when the author’s companion, the zoologist Lary Shaffer notes that ‘Ebola... if this one breaks out we’re also in deep trouble... It’s just for Homo sapiens. It’s adapted to take advantage of our caring for the dead. It’s in there at the funeral service.’

The latest outbreak began in December 2013 with the death of a two-year-old girl from unidentified haemorrhagic fever in Guinea. By March 2014 it had spread to Sierra Leone and wider throughout Guinea. Other cases have occurred in Nigeria, Mali and Senegal. The fatality rate is around 50 per cent. So far, the WHO has documented 21,261 cases of Ebola, of which 8,414 died.

A smaller, almost entirely unreported outbreak in the DRC was contained. ‘In places like the Congo, Gabon, Sudan, people have come to learn how to deal with outbreaks and isolate people,’ says Leach. ‘Most small outbreaks die out. What happened in West Africa is very different.’

A CHANGE IN THINKING

Global development, such as the intensification of livestock and climate change may also be influencing the way such diseases affect society. ‘Some of the geography that affects how disease emerges and spreads are to do with ecological and livelihood factors, how climate change and other issues affect how people, livestock and microbes interact,’ says Leach. ‘There has been a lot of irrigation in the Rift Valley which can be argued is good for development. But it has turned Rift Valley Fever from an episodic issue into an endemic one as there is now a large body of water for mosquitoes to breed in.’

Such changes in human and physical geography make a pressing case for a change in the mindset of the West towards global health care, according to Aurelia Nguyen, director of policy & market shaping at Gavi Alliance, a vaccine alliance of public and private sectors. ‘The nature of globalisation and urbanisation means that obscure diseases from obscure places are unlikely to stay that way,’ she says.

It’s only fair to highlight the enormous achievements of immunisation: the eradication of smallpox; polio cut by 99 per cent; and reduced illness, disability and death from diphtheria, tetanus, whooping cough, measles, Haemophilus influenza type b disease, and epidemic meningococcal A meningitis.

There has also been steady progress against the biggest killer of all – malaria. The WHO reports that deaths from malaria have fallen dramatically since 2000. According to the WHO’s World Malaria Report 2014, between 2000 and 2013, the malaria mortality rate decreased by 47 per cent worldwide and by 54 per cent in Africa – where 90 per cent of malaria deaths occur. Across sub-Saharan Africa, despite a 43 per cent population increase, the number of people infected fell from 173 million in 2000 to 128 million in 2013. A global stockpile of two million doses of oral cholera vaccine has also been created, to help control cholera epidemics.

Yet even success stories can be looked at in two ways. In 2012, bedaquiline, the first tuberculosis drug for 40 years was approved. Wonderful news? Or a scandal that it took so long? After all, TB still kills 1.4 million people a year.

Meanwhile, a spokesperson for the vaccinations wing of the WHO says that, contrary to public perception, work on Ebola vaccines preceded the current outbreak. Leach, however, points out, that much of this research was sponsored by the US and Canadian military, in pursuit of stockpiles in lieu of a bio-terrorist attack. ‘That could be a good thing, as it garners attention for the vaccine, but it also means that the issue is approached from a certain direction,’ she says.

A technician of the PNLTHA mobile team works on some villagers' samples, during a visit at the village of Mpata, DR Congo (Image: Benoit Marquet)

FINDING THE MONEY

Underpinning the debate is the fact that, right across the planet, vaccines are almost entirely manufactured by private companies. Generally, R&D for vaccines is funded by public money, either through universities or public institutions such as the US National Institutes of Health. This research is then picked up by pharmaceutical companies that make a judgement on whether to develop the drug or vaccine.

‘The global system for R&D depends on market incentives and intellectual property rights,’ says Kamal-Yanni. ‘If you hold the intellectual property rights you don’t just want a price, you want the highest possible price. Intellectual property has been a holy cow. Pharmaceutical companies put horrendous figures on R&D. They say it costs $2.7billion to put a drug on the market. But we don’t have access to the data because companies say it is commercially confidential.’

In January, MSF issued a report, The Right Shot: Bringing Down Barriers to Affordable and Adapted Vaccines, that showed how, in the poorest countries, it now costs 68 times more to vaccinate a child than it did in 2001.

Central to the issue, says Potet, is that the business model is based on the ability of the patient and the country to pay a high price. ‘In the case of Ebola, that capacity was thought to be limited, so the market was limited. That’s the basic reason why pharmaceutical companies have not invested much in this area. The economic model of pharmaceutical companies is not appropriate for emerging or neglected diseases.’

Other models have been introduced, but they can be imperfect, says Potet, who cites the Priority Research Voucher scheme, launched by the US Food and Drug Administration in 2007. This invites pharmaceutical companies to develop vaccines for neglected diseases such as leishmaniasis. In return, they receive up to $100million in kind. Effectively this is a voucher they can use to fast-track registration of an unrelated, but more lucrative drug – a huge commercial advantage. ‘It’s a good idea,’ says Potet, ‘but there is no requirement for the company to guarantee the neglected disease vaccine price will not be set too high.’

Research into the Ebola vaccine, meanwhile, is being funded from a variety of means, including the Wellcome Trust in the UK, while Gavi has pledged to pay up to $300million to procure the vaccines, in order to guarantee the manufacturers turn a profit.

‘It is the right thing to do,’ says Kamal-Yanni, ‘but you can’t help thinking if this would have happened were there no danger to the West. But they can make the luxurious claim they are doing it for the good of humanity.’

Nguyen stresses that Gavi’s commitment was conditional on drugs manufacturers taking a longer term view. ‘Yes, we are faced with a terrible crisis, but let’s make clear we do not expect to be in the same situation down the line,’ she says. ‘It was Ebola today, but it could be a number of other diseases tomorrow. How do we make sure we don’t have such a scramble every time an outbreak happens?’

ATTITUDE SHIFT

Does the belated research into an Ebola vaccine provide a model that can be more widely applied to neglected diseases? Observers believe this would require a significant shift in attitudes and funding. ‘The current business model for vaccines will not address this,’ says Potet. ‘The existing set up has created the need for ad hoc products, such as is happening with Ebola.’

So can research and development be financed in a different way? For many years, Oxfam proposed a global pool of money raised by a percentage of GDP from every country, which could be invested collaboratively, but it proved unsuccessful diplomatically and was opposed by the private sector, according to Kamal-Yanni.

‘In the end I don’t think pharmaceutical companies are ever going to back these [new initiatives],’ says Leach. ‘They are private companies, they want to make a profit. So it comes back to public funding, or judicious public-private partnerships.’ Other initiatives have sought to fill in the gaps when commercial profits are not there to be cherry picked. The Global Alliance for TB Drug Development was set up in 2000 as a not-for-profit product development at a time when no TB drugs were in clinical development. This has, it says, ‘reinvigorated global TB drug development’ that can ‘bridge the gap between market opportunities and peoples’ needs’ by drawing on the resources of public, private, academic and philanthropic sectors.

For MSF, the tipping point came a decade ago when the private sector developed a drug for sleeping sickness. ‘The mainstay was a drug derived from arsenic,’ says Potet. ‘It was relatively effective but it killed five per cent of patients. That made it difficult for us to make the decision in the field to administer the drug.’ For MSF this epitomised the shortcomings of vaccines for neglected diseases. ‘There was just very limited research, again these people are very poor, so the companies were not really incentivised,’ says Potet.

MSF’s response to this was to help establish the DNDi. Before engaging with pharmaceutical companies, MSF identifies the needs in the field, what patients, governments and health care workers really required. Then drugs companies were asked to open their archives of chemical compounds to match them against neglected diseases. If they proved promising, the licence was purchased by DNDi on a not-for-profit basis. So far this has yielded a non-arsenic based vaccine for sleeping sickness.

ANIMAL INSTINCTS

Exotic animal diseases such as Newcastle Disease and Rift Valley Fever have a pernicious effect on communities in the developing world, where up to 900 million people depend on livestock for food security, nutrition, and transportation. In Africa, where up to 50 per cent of cash income is derived from livestock, around 25 per cent of this livestock dies annually from treatable animal diseases, some of which can jump to humans.

Vaccines often exist, but the high cost of doing business in small, diverse and fragmented markets is unprofitable for pharmaceutical companies. The gap cannot be filled locally because many developing countries lack the capacity to produce or license such drugs.

‘Demand and supply weren’t meeting each other,’ says Dr Alan Tollervey, head of the agriculture team at the UK government’s Department for International Development, which established a not-for-profit company that could broker these linkages, called GALVmed (Global Alliance for Veterinary Medicines).

GALVmed uses public money to work with both the public and private sector to deliver drugs and vaccines in a way which poor farmers are able to pay for. The key donor has been the Bill and Melinda Gates Foundation, which in 2012 announced a further £26million investment. Much of the chain – vaccine manufacturer, distributors, packers – was put together by tender, by engaging with local businesses and communities, local pharmaceutical companies and research institutions.

GALVmed operates in 15 countries in Africa, two in Asia and has more than 120 partnerships with research and private sector partners. It has also overseen the vaccination of more than 450,000 cattle in Kenya, Tanzania and Malawi against East Coast Fever and sold ten million doses of Rift Valley Fever vaccine.

More than 610,000 birds in 100,000 village houses have also been vaccinated against Newcastle Disease and a further 21 products for 12 animal diseases are already in the pipeline.

LESSONS TO BE LEARNT

Despite these measures, no-one is predicting a diminishing role for multinational pharmaceutical companies. ‘Scale is important for vaccine economics,’ says Nguyen. ‘You need sterility [for production] and there are long lead in-times. That all needs pretty deep pockets.’

Despite several requests, GlaxoSmithKline (GSK) did not provide a response to any of the issues raised in this article. The company has donated £10million to the Tres Cantos Open Lab Foundation, which it established as an independent not-for-profit organisation. Here, scientists can test ideas on an industrial scale. Projects are focused on early stage drug discovery and include efforts to develop novel classes of medicines for malaria and multiple drug resistant TB.

The WHO maintains a determinedly upbeat note. In the introduction to its Global Vaccine Action Plan it argues that ‘this century promises to be the century of vaccines, with the potential to eradicate, eliminate or control a number of serious, life-threatening or debilitating infectious diseases, and with immunisation at the core of preventive strategies.’

Potet believes the Ebola outbreak may well have changed attitudes. ‘I wasn’t optimistic until the recent outbreak, but a lot of attention has been paid to the suffering in West Africa,’ he says. ‘I hope that Ebola will be a turning point. I think lessons will be learnt to promptly respond to emerging outbreaks and pathogens, irrespective of where they happen.

‘If there is political motivation to address the model of pharmaceutical companies then we may see a historic change in the treatment of neglected diseases,’ he continues. ‘We can hopefully capitalise on this outbreak and make sure that such interventions and drive become the rule, not the exception.’

Leach also believes priorities may have shifted. ‘This outbreak has been global enough and profound enough that it could be a catalyst for new thinking,’ she says. ‘We need to understand the drivers that are really important to keep going once this particular outbreak of Ebola is wrapped up. We need to give a priority to health systems, and we require a geographical understanding of the environmental, health and social factors, and how they all relate. Global health has to be seen as a public good.’

Looking at the Western hysteria over Ebola, Kamal-Yanni believes it should serve as a reminder of what needs to be put in place with diseases that are much more easily transmitted. ‘You have to go out and get bitten by a mosquito to get malaria. You have to touch a dying or dead person to get Ebola. You can get SARS just by standing at a bus stop,’ she points out.

‘People are resilient,’ she adds. ‘But if you leave people to themselves, they will take years and years to bounce back. Unless there is long-term investment from outside to help with practical issues such as raising taxes, there will be an economic and social disaster. Ebola should be a turning point in the way we think about medicines and vaccines. Ill-health is not about people ‘over there’, that we can give a bit of charity to and leave them to it. We need to develop these vaccines and remember that they can also hit us.’

Meanwhile, others take a more pessimistic position. ‘I’m not confident we are heading in the right direction,’ says Nguyen. ‘I’m concerned that – as this Ebola outbreak hopefully decreases – other unrelated topics come to the centre of people’s minds and we revert to business as usual. A small scientific community will work away at this issue, but the global mobilisation we’ve seen will die down. It’s incumbent on everyone to reflect on why that is a risk.’